Litter has become a common component of marine ecosystems, and its assessment and monitoring are now of primary interest. Here, we characterized seafloor litter in the mesophotic depth range of the Ligurian Sea, one of the most urbanized basins of the Mediterranean Sea. Eighty sites (30-220 m depth) were investigated by by means of ROV video transects. Data regarding environmental parameters and anthropic pressures were used to explain the distribution of human-derived objects. Litter resulted widely distributed in all the investigated areas, with maximum densities of 7900 items ha-1. It was mainly represented by abandoned fishing gears, with highest abundances found on the deep coastal rocky shoals exploited by artisanal and recreational fishermen. Urban litter, primarily represented by plastics, was generally higher close to shore, especially near river mouths and large harbors. Litter densities reported here are among the highest ever recorded in Europe, denoting the urgency for specific actions to prevent further spreading.